The over-all objective is to further our understanding of the cellular and biochemical basis of corneal ulceration and repair so that it will be possible to prevent loss of vision. Cell and tissue culture methods and in vivo models will be used to study the role of the plasminogen activator-plasmin system in the chemotaxis of polymorphonuclear leukocytes, in the secretion and activation of latent corneal collagenase, and in neovascularization. Cell culture will be used to obtain latent collagenase that will be purified to homogeneity. Methods of protein chemistry will be used to study the mechanism of activation of the latent enzyme. Specific anti serum to the enzyme will be raised and will be used to localize collagenase during ulceration in model systems. In vitro "coupled" system will be developed to study the synthesis, secretion, activation, and will be developed to study the synthesis, secretion, activation, and clearance of corneal collagenase. The role of progestational hormones in regulating collagenase in herpetic stromal keratitis will be investigated. Collagen degradation occurs in various pathological situations as in destructive joint disease, periodontal disease, tumor spread, and corneal ulceration. In addition, localized, controlled collagen degradation occurs in normal physiological situations like uterine involution, bone remodelling, and possibly vascularization. Although the specific manifestations of collagen degradation depend on the organs involved, the basic mechanisms of collagen resorption appear to be common to the different normal and pathological situations. Contributions to an understanding of the mechanisms of corneal ulceration no only facilitate our ability to prevent ulceration, but also suggest possible means of therapeutic intervention in the collagen degradation which occurs in other pathologies.